tbuckley/cabot-search huggingface dataset:
Prognostic biomarkers for survival in mucosal melanoma.
Authors: Julia Cara Thierauf, Stefan T. Kaluziak, Elizabeth Codd, Stacey Dybel, Soma Jobaggy, Rashi Purohit, Alex Farahani, Aikaterini Dedeilia, Vivek Naranbhai, Mai Hoang, Adam Fisch, Lauren Ritterhouse, Genevieve Marie Boland, Jochen K. Lennerz, A. John Iafrate
Journal: Journal of Clinical Oncology (2023)

e21576 Background: Mucosal Melanoma is a rare subtype of melanoma with a more aggressive clinical course when compared to cutaneous melanoma. In cutaneous melanoma, the absence of pigmentation and presence of NRAS/KRAS mutations are known as biomarkers indicating an aggressive clinical course with significantly shorter overall survival times. Similar data for mucosal melanoma are currently missing. Here, we present real world outcome data in a large cohort of genotyped mucosal melanoma patients and assessed the prognostic relevance of pigmentation- and NRAS/KRAS mutation status. Methods: We correlated pathological reports and clinical data with overall survival of patients with mucosal melanoma. Furthermore, we performed clinically integrated molecular genotyping and analyzed real world treatment regimens for covariates associated with clinical outcome. For institutional data analysis, we ran a source query and only included patients with the diagnosis of mucosal melanoma, available genotyping data and comprehensive clinical information. As a population-based reference and to directly compare overall survival differences we first queried the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database. Pigmentation status was assessed by pathological review. Treatment regimens were identified by chart review. Results: We identified a cohort of 39 patients with mucosal melanoma where clinical and molecular data was available. Patients with amelanotic mucosal melanoma had a significantly shorter overall survival ( p = 0.003). In addition, the presence of a NRAS or KRAS mutation was significantly associated with poor overall survival (NRAS or KRAS p = 0.024). Therapeutic regimens were heterogeneous with a mean of 5 treatment lines per patient. Patients with low stage tumors who received immunotherapy had a significantly shorter overall survival (p &lt; 0.001), although numbers were small. Conclusions: The absence of pigmentation and the presence of NRAS or KRAS mutations are poor prognostic indicators for survival in CM. Both biomarkers are have been described in MM. Currently, it is unknown if the same prognostic relevance for the lack of pigmentation and RAS mutations exists in MM. Here we analyzed a cohort of MM for outcome measures and determined that two known prognostic biomarkers for CM are in fact novel prognosticators for MM.
Somatic aberrations detected in tumor tissue and plasma in Chinese patients with stage I single-lesion and multi-lesions lung cancer.
Authors: Guotian Pei, Yingshun Yang, Mingwei Li, Xiaoxue Ma, Jiayue Qin, Shanbo Cao, Qiang Liu, Shuai Wang, Yuqing Huang
Journal: Journal of Clinical Oncology (2023)

e20600 Background: Recent studies show that the use of circulating tumor DNA (ctDNA) has potential to guide precision medicine and transform the management of early-stage lung cancers. We aim to investigate whether plasma is suitable for detecting tumor‐derived DNA in patients with stage I single-lesion lung cancer and multifocal lung cancer which has rarely been investigated. Methods: Matched tumor tissues (n = 114) and plasma samples (n = 95) from Chinese patients with stage I lung cancer (n = 95), including 80 patients with single-lesion and 15 patients with multiple primary lung cancer (MPLC) diagnosed by American College of Chest Physicians (ACCP) guidelines, were analyzed by Acornmed panel with 808 cancer-related genes. Results: Using tumor tissue-based results as the gold standard, we performed variant-level assessment of the ctDNA tests. In patients with single-lesion, sequencing detected alterations in 98.8% (79/80) ctDNA and 9.3% (74/797) of variants in ctDNA were detected by corresponding tDNA. Among them, 31.3% (25/80) patients had at least one overlapping variant called by tDNA and ctDNA, and 5% (4/80) patients shared EGFR in both tDNA and ctDNA. Meanwhile, we identified 2 mutated EGFR in ctDNA that were not detected in tissues. As for multiple primary lung cancers, 86.7% (13/15) of MPLC patients had ≥1 alteration in ctDNA. In addition, 7.4% (9/122) of variants in ctDNA were detected by corresponding tDNA in MPLC. The overall concordance for all variants detected in both ctDNA and any tDNA of patients was 53.3% (8/15) in MPLC, with EGFR and KRAS as the most two frequent mutations. Furthermore, mutations consistent with ctDNA were detected in 29.4% (10/34) of the lesions in MPLC. Conclusions: Our analysis showed that plasma with high mutation detection rate and considerable concordance rate with tDNA maybe a powerful complement to tissues for molecular testing in lung cancer. Furthermore, ctDNA detection not only may be able to overcome the heterogeneity of tumors but also more comprehensively reflect the disease state of patients with multifocal lung cancer.
Clinicopathological features and treatment patterns of patients with cancer of unknown primary site (CUP): Mayo Clinic experience.
Authors: Sandra Algarin Perneth, Riham Suleiman, Mayra Duran, Ricardo Loor Torres, Cristian Soto Jacome, Jennifer Gile, Roberto Antonio Leon-Ferre, Jose Caetano Villasboas, Rondell P. Graham, Stephan Thome, Thorvardur Ragnar Halfdanarson, Harry E Fuentes Bayne
Journal: Journal of Clinical Oncology (2023)

e18803 Background: CUPs are a heterogeneous group of metastatic cancers for which a standardized diagnostic work-up fails to identify the site of origin at the time of diagnosis. CUP accounts for 3%-5% of all cancer diagnoses worldwide, and the natural history of patient with CUP differs from that of patients (pts) with cancer with known primary tumor. Here we report and summarize the clinical features of patients with CUP treated at Mayo Clinic. Methods: Retrospective study of patients treated at Mayo Clinic Rochester MN from 2010 to 2021. Patient demographics, tumor-related variables, treatment-related variables, and clinical data were extracted. Descriptive statistics were used, and all data were analyzed by the SPSS version 22.0 software (SPSS, Chicago, IL, United States). Results: From a total of 214 pts, 207 pts were included, as primary tumor site was identified in 7 patients after initial evaluation. The pts in this study were predominantly white (87%) of female (50.2%) gender with a mean age of 63 (SD: 13) without history of smoking (51%) and either private or public insurance (82.6%). The predominant histology was adenocarcinoma (30%), followed by neuroendocrine neoplasms (27%), and carcinoma NOS (not otherwise specified) (25%). The most prevalent grade in this cohort was grade III with poorly differentiated tumor cells. All pts had diagnostic imaging and the most used imaging modalities included CT (81.2%), and PET-CT (43.5%). In our cohort, the 3 most common sites of metastases included lymph nodes (57.5%), liver (37.8%), lung (34.3%), and bone (23.7%); and in 64% of pts, there was a specific presentation pattern including liver-predominant (24.6%), lymph node-predominant (24.6%), bone-predominant (7.7%), and peritoneal carcinomatosis (7.7%). The majority of pts received systemic therapy (69%) as first line of therapy and the most frequent first line regimens included platinum-doublet (26.5%), gemcitabine-based regimen (20.7%), 5FU-based regimens (18%) and somatostatin analogs (16.7%); whereas salvage radiation and ablation were offered to 11% of pts and surgery to 17%. The median follow-up time was 22 months (IQR: 45) with a median survival time of 23 months and the 3-year cumulative survival rate was 30%. Conclusions: The heterogenous nature of CUPs and lack of specific immunohistochemical signature prevents primary tissue of origin diagnoses in CUP pts. Without the identification of a primary origin site, treatment is restricted to generic chemotherapy with limited benefit as demonstrated in this cohort.
The utilization of cryopreserved sperm in males with cancer.
Authors: Anna Claire Reynolds, Luwam Ghidei, Jordan Kassab, Kevin Campbell, John Sullivan, Larry Lipshultz, Laurie Mckenzie
Journal: Journal of Clinical Oncology (2023)

e18791 Background: Ten percent of individuals diagnosed with cancer in the United States are under age 45. Fortunately, improvements in cancer therapy have enabled younger individuals to survive with cancer related deaths decreasing steadily over the past 20 years. The American Society for Clinical Oncology (ASCO) recognizes the importance of future family building for cancer survivors and states healthcare providers should discuss fertility preservation options prior to cancer treatment initiation. Despite these recommendations, the data regarding survivor utilization of cryopreservation sperm is limited. The aim of this study is to assess factors that impact the post treatment utilization of cryopreserved sperm. Methods: 721 patients who underwent sperm cryopreservation for cancer indication from 1/1/2010 – 10/1/2020 at a single institution were included in the retrospective chart analysis. Cancer diagnosis, patient age at time of sperm banking, sample storage duration, and sample disposition were collected. Sample disposition included utilization for pregnancy effort(s), request to discard and/or donate to research, and lost to follow up. Descriptive statistics were employed via Excel. Results: Fifty-two of 721 (7.21%, 95% CI 5.4-9.4%) patients utilized their sperm samples for fertility treatment, and 104 patients (14.42%) subsequently requested their samples be discarded. When stratified by age at time of sperm banking, men who banked between the ages of 36 and 40 years had the highest rate of sample utilization for pursuing fertility treatment (12/68, 17.65%, 95% CI 9.5-28.8%). Importantly, those that cryopreserved sperm and subsequently discarded the samples ranged from 8.97% (21 to 25 years) to 28.13% (41 to 45 years). When analyzed by diagnosis, patients who utilized their samples for fertility treatment had varying cancer diagnoses with percent utilization ranging from 4.11% (skin/connective tissue/musculoskeletal cancers) and 20.0% (lung cancer). Overall, 75.59% of the samples collected are unutilized (545/721, 95% CI of 72.3-78.7%). Only 3% were lost to follow up, defined as inability to contact patient after three attempts. Conclusions: Cryopreserved sperm is widely underutilized with only 7.21% of patients utilizing the samples for future conception. Men between ages 36 to 40 years at time of banking are most likely to utilize their samples and utilization varied by cancer diagnosis. This large cohort (with less than 5% lost to follow up) highlights the importance in identifying additional predictors of cryopreserved sperm utilization in cancer survivors. [Table: see text]
Association between symptoms and health-related quality of life in patients with cancer with prior or ongoing immune checkpoint inhibitor therapy exposure.
Authors: Salene M.W. Jones, Anissa Chan, Emily Enright, Aleksandra Raczka, Vivian Nguyen, Shailender Bhatia, Scott S. Tykodi, Joshua Veatch, John A. Thompson, Sylvia Lee, Matt Lashey, Evan Thomas Hall
Journal: Journal of Clinical Oncology (2023)

e24085 Background: There is a growing appreciation that patients exposed to immune checkpoint inhibitors (ICI) may experience long-term symptoms that impact health-related quality of life (HRQoL). We conducted an app-based, electronic patient reported outcomes (ePRO) study to explore the relationship between the symptom experience and HRQoL in a population of patients with cancer exposed to ICI therapy. Methods: Eligible patients had a history of advanced skin cancer or kidney cancer treated with ICI (adjuvant or metastatic) with ongoing, clinician-assessed disease control. Patients may have completed a course of ICI or continued on therapy if ≥ 6 months had passed since initiation. We conducted a single-center, observational, prospective cohort study where participants completed ePRO assessments via smartphone (ImmunoWave) measuring eleven symptoms (PRO-CTCAE) and HRQoL (PROMIS-29) weekly for 12 weeks. We used generalized estimating equations to assess the changes in PROMIS scores over study and to test the association of PRO-CTCAE symptoms with PROMIS scores and subdomains. Results: Forty-seven patients (77% melanoma, 15% renal cell carcinoma, 8% non-melanoma skin cancer) consented to the study. 70% were on active therapy while 30% had completed therapy. Most (62%) were treated in the metastatic setting. 43 patients who completed questionnaires were included in the analysis. Among subdomains of HRQoL at the study population level, social function was observed to have a significant linear trend (p = 0.013) and potentially meaningful (3.9 points overall) increase over the 12 weeks. Other subdomains were felt to have no clinically meaningful change at the population level over the 12 wk study period. Several PRO-CTCAE symptoms were significantly associated with health-related quality of life (PROMIS) subdomains (Table). Joint pain was significantly associated with fatigue (B = 1.006, p = 0.045), pain interference (B = 2.579, p = 0.002) and physical function (B = -1.532, p = 0.042). Itch was associated with anxiety (B = 1.017, p = 0.007) and social function (B = -1.136, p = 0.030). Numbness and tingling was associated with fatigue (B = 0.891, p = 0.027) and sleep disturbance (B = 1.436, p &lt; 0.001). Conclusions: We observed high concordance between patient symptom report by PRO-CTCAE and corresponding PROMIS HRQoL subdomains. Addressing specific symptoms such as itch, numbness/tingling and joint pain in patients with current or prior ICI exposure could improve HRQoL. [Table: see text]
Clinician-patient insights and alignment on urothelial carcinoma care.
Authors: Tariqa Ackbarali, Stephanie Chisolm, Scott T. Tagawa, Neal D. Shore
Journal: Journal of Clinical Oncology (2023)

e18755 Background: The expansion of the treatment landscape for urothelial carcinoma (UC) including immune checkpoint inhibitors and antibody-drug conjugates (ADCs) hold the promise of improving long-term survival in patients with more advanced disease. A tethered (patient-clinician) educational initiative was designed for patients/caregivers to stay up-to-date with new therapies and for clinicians to facilitate integration of new therapies into clinical practice. Methods: Two, 1-hour online, interactive, video-based programs were designed for patients and clinicians. The patient/caregiver program was hosted on CancerCoachLive in January, 2022 and the clinician program on UroCareLive and OMedLive in December, 2022. The initiative was conducted in collaboration with LUGPA, Large Urology Group Practice Association and BCAN, Bladder Cancer Advocacy Network. Behavioral assessment of preferences and attitudes toward managing patients were examined throughout the CME series and patient/caregiver program. A planned analysis of the data from these questions determined patient and clinical impact. Outcomes from the patient program were analyzed and presented during the CME series followed by expert-identified strategies to improve clinical practice. Results: A total of 1,071 participants have engaged across both educational programs. The majority of the patient participants were in remission or had recurrent UC. Patients provided insight on what mattered most at the point of decision-making (48%), the symptoms that led to a diagnosis – hematuria (85%), and their greatest quality-of-life challenge – urinary functioning concerns (52%). Of those who have been treated previously, 83% were treated with an immunotherapy and 9% with an antibody drug-conjugate. Pre- to post-activity comparisons demonstrate a greater likelihood of participation in clinical trials. When asked about the challenges patients with UC face, the top 3 challenges identified by patients were not aligned with those identified by clinicians. Clinicians additionally identified themselves as lacking confidence (58%) in their understanding of patient’s concerns or challenges. Following the activity, clinicians were very motivated to address these concerns (88%). Clinicians identified enfortumab vedotin (44%) as the ADC with the greatest potential to improve patient outcomes and a lack of knowledge on evidence-based strategies as the primary barrier to implementing changes in practice (34%). Qualitative data from both the patient and clinician activities were captured representing write-in examples of behavioral impact which will be shared. Conclusions: The initiative contributed to the provision of valuable patient insights, patient-clinician misalignment, and clinician confidence addressing patient concerns. Increasing this awareness fostered practical strategies and discussion to improve patient-centered care.
Tissue and plasma-based mechanisms of resistance to first-line osimertinib in EGFR-mutant NSCLC: A multi-institutional cohort.
Authors: Zofia Piotrowska, Lanyi Nora Chen, Elaine Shum, Cathleen Park, Matthew Guo, Ying Liu, Misha Tran, Jennifer Aline Marks, Mandeep Banwait, Stephen V. Liu, Susan Combs Scott, Christine M. Bestvina, Jonathan W. Riess, Kristen A. Marrone, Richard Delmar Hall, Ryan D. Gentzler, Catherine A. Shu
Journal: Journal of Clinical Oncology (2023)

9108 Background: Osimertinib (osi) is the preferred 1 st line (1L) therapy for patients (pts) with EGFR+ NSCLC, but acquired resistance is universal. Identification of mechanisms of resistance (MoR) to 1L osi can inform subsequent therapies. We report a retrospective, multi-institutional cohort of pts with tissue biopsy (TBx) and/or liquid biopsy (LBx) upon 1L osi progression (PD). Methods: Pts with advanced EGFR+ NSCLC who had TBx and/or LBx (for ctDNA analysis) obtained at PD on 1L osi at 8 participating institutions were included. Molecular testing was performed using next-generation sequencing (NGS) and, in a subset, FISH per local standards. We retrospectively collected clinical characteristics, tissue histology, NGS/FISH results and subsequent therapies. Results: 193 pts (128 female; median age 64 yrs) had TBx (n = 129) and/or LBx (n = 122) upon PD on 1L osi, 58/193 had both tissue and ctDNA. Primary EGFR mutations included del19 (102), L858R (76), and other (15). Median time from osi start to first bx was 14 mos (range, 1-55). MoRs are summarized in the table. In all, 86/193 (45%) pts had a known MoR identified on TBx and/or LBx. Among 129 pts with TBx, histologic transformation (trans) and MET amplification (amp) were the most common MoR, each seen in 16% pts. Among 122 pts with LBx, secondary EGFR mutations were the most common MoR, seen in 15%. Among the 58 pts with both TBx + LBx, discordance between major MoRs was seen in 21/58 pts (36%), most commonly due to histologic trans detected on TBx only (n = 7) and discordant MET amp status (n = 8; 6 TBx+/LBx-, 2 TBx-/LBx+). No MoR was identified in 53% TBx and 75% LBx (including 14% Lbx where the original EGFR mutation was not detected in ctDNA). Results of TBx led to MoR-directed 2L therapy in 41/129 (32%) pts, while LBx results led to MoR-directed 2L therapy in 16/122 (13%). Conclusions: In this large, multi-institutional cohort, histologic trans (16%) and MET amp (16%) were the most common MoR to 1L osimertinib on tissue bx. In ctDNA, secondary EGFR mutations (15%) were the most frequent MoR. The results of TBx were more likely to impact second-line therapy than LBx. Our results underscore the importance of tissue biopsy (and limitations of liquid biopsy) after osimertinib PD, where tissue testing remains the gold standard. In addition, with more than half of patients having no identifiable MoR despite comprehensive testing, our results highlight the need for MoR-agnostic treatment strategies. [Table: see text]
Faith-based communities’ preferred interventions to improve the participation of black/African-American persons in medical research and clinical trials: A focus group study.
Authors: Heather McKee Hurwitz, Pamela Combs, Mark Ribbins, Minh-Tri Nguyen, Kimberly Sanders
Journal: Journal of Clinical Oncology (2023)

e18648 Background: A variety of interventions within faith-based and medically underserved communities have been utilized to increase racial/ethnic minorities’ participation in health programming and clinical trials. However, the literature lacks studies on which interventions are preferred by church members and leaders to address disparities in clinical trials. Methods: The study utilized focus groups to understand participants’ knowledge and attitudes about medical research/clinical trials and to develop and appraise interventions for and in collaboration with members and leaders of predominately Black/African American faith-based organizations. Participants were recruited by convenience and snowball sampling from organizations involved in the Cleveland Clinic Taussig Cancer Center Community Outreach program’s faith based model called, Stopping Cancer In Its Tracks (SCIIT). Study personnel conducted 6 focus groups at 6 different churches from June through August 2022. Results: 30 participants joined the study. Conversations lasted 90-120 minutes and covered a range of topics. Each group included deep, cathartic sharing about disparities in accessing medical/cancer care and racism, particularly within medicine. Participants explained that low enrollment among Black/African-Americans in clinical trials is a result of everyday and structural racism. Also disparities are linked to the compounded, long-term lack of beneficence or human rights within research and health care for their communities. Accordingly, diversity in clinical trials may improve by creating interventions that address distrust, communication, and information and access gaps, and are tailored to each church. Preferred interventions should: 1) Embody a deep, long-term, relationship-building process. 2) Focus on creating trust by sharing in church services/activities/meals/two-way conversations/cancer screenings. 3) Leverage testimonials from cancer survivors who have participated in clinical trials. The focus groups themselves were felt by participants to be an example of the trust building and knowledge sharing necessary to address disparities. Participants expressed interest to develop interventions in partnership with the study personnel of health care workers. Conclusions: The study fills a gap in the literature by analyzing and amplifying the ideas of Black/African-American church members and leaders from medically underserved communities who generally have been excluded from research. Participants preferred interventions that feature long-term relationship building and engagement. Future research should implement and test the effectiveness of these interventions.